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Learning Objectives

identify the primary drug for treatment of chronic beryllium disease (CBD), and

describe possible sequelae of CBD.

Introduction

Although CBD is treatable, there is no cure for CBD. The goal of treatment is to reduce morbidity and mortality.

Who Should Be Treated?

For patients with impairing CBD, corticosteroid therapy continues to be the primary treatment modality (Glazer and Newman 2003). Patients who are sensitized to beryllium but do not yet have the disease do not need any treatment. However, they do need regular exams to detect early signs of disease, as well as early and aggressive treatment of respiratory infections. Patients who have early beryllium disease but do not yet have symptoms may not require treatment. However, they need to be medically monitored. Some people who are detected at the early stages may go many years without needing treatment. Patients with beryllium disease who have abnormal or deteriorating pulmonary functions are usually treated with prednisone.

Treatment with Prednisone

Patients with evidence of early lung damage are treated with 40 mg of prednisone on a daily or alternate day regimen for 6 months. Prednisone is tapered by no more than 10 mg every other month to the lowest dose possible without evidence of renewed disease activity. Treatment with prednisone often stabilizes the disease and improves symptoms. Disease activity is monitored by the same tests that demonstrated deterioration. The lowest dose of prednisone that prevents disease progression should be maintained (Rossman 1996; Maier et al. 2001).

Monitoring the Disease

Unfortunately, lifelong therapy is usually required, since the disease recrudesces with reduction of the corticosteroid dose. Oral methotrexate and azathioprine have been used as corticosteroid-sparing agents by some clinicians (Glazer and Newman 2003; Muller-Quernheim et al. 1999). Before initiating corticosteroid therapy, a baseline chest radiograph, high resolution CT, complete pulmonary function tests (including lung volumes, spirometry, and diffusing capacity), and exercise testing, with arterial blood gas measurements, should be performed. Patients should be monitored for therapy-induced side effects on an ongoing basis.

Adjuvant Therapy

Adjuvant therapy with bronchodilators, diuretics, and oxygen should be considered as well. Supplemental oxygen may be necessary to correct hypoxemia associated with CBD. Right ventricular failure and its complications are late-stage sequelae. Pneumothorax can occur (Glazer and Newman 2003; Rossman 1996). Supportive therapy may also include pulmonary rehabilitation to maintain muscle strength and tone, vaccinations to prevent influenza and pneumococcal pneumonia, and antibiotics for acute infections.

Possible Sequelae and Management Considerations

Pulmonary fibrosis, which is common in long-term disease, is poorly responsive to corticosteroids. As with chronic lung disease of other etiologies, one should evaluate for bacterial respiratory infections and should treat infections promptly with antibiotics when indicated, especially for those on immunosuppressive therapy. Patients should be immunized against Pneumococcus and influenza and counseled to avoid exposures to other substances that cause lung injury, including cigarette smoke (Glazer and Newman 2003; Rossman 1996). Right ventricular failure and its complications are late-stage sequelae.

Importance of Early Detection and Treatment

In contrast to most occupationally related lung disease, the early detection of CBD is useful for several reasons. First, measures can be put in place to limit further beryllium exposure. Secondly, treatment can lead not only to regression of the signs and symptoms, but also should prevent further progression of the disease. The management of CBD is based on the hypothesis that suppression of the hypersensitivity reaction (the granulomatous process) will prevent the development of fibrosis. However, once fibrosis has developed, therapy cannot reverse the damage (Rossman 1996).

Preventive Measures

Primary preventive measures include skin protection and minimizing airborne exposures to prevent sensitization. Because beryllium sensitization (BeS) and CBD are immune-mediated processes, future exposures should be minimized for all affected patients and all workers. Some reports suggest that removal from exposure has lead to clinical improvement in select patients (Glazer and Newman 2003; Glazer and Newman 2004; Sood et al. 2004). It appears that BeS can occur after a short period of exposure, but beryllium disease may require a longer latency and/or period of exposure (Henneberger et al. 2001). The lack of a clear dose response for the development of CBD implies that early identification of sensitization and removal from exposure may reduce the development of CBD (Judd et al. 2003; Kelleher et al. 2001).

Dermatologic Management

Primary preventive measures such as avoiding skin contact with beryllium to prevent sensitization are key. Careful irrigation and debridement are recommended for wounds potentially contaminated with beryllium. Beryllium particles imbedded in the skin often must be removed before skin wounds will heal. Complete excision is curative for beryllium-contaminated injury sites that demonstrate delayed healing, ulceration, and granuloma formation. The main treatment for contact dermatitis associated with beryllium salt exposure is cessation of exposure (Berlin et al. 2003).

Key Points

Primary preventive measures such as skin protection from and minimizing airborne exposures to beryllium are key to preventing sensitization.